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Journal of Oncology
Volume 2015, Article ID 571739, 14 pages
http://dx.doi.org/10.1155/2015/571739

Review Article
Dental Treatment in Patients with Leukemia
Caroline Zimmermann,1 Maria Ins Meurer,2,3
Liliane Janete Grando,2,3 Joanita ngela Gonzaga Del Moral,4
Ins Beatriz da Silva Rath,5 and Silvia Schaefer Tavares6
1

Graduate Program of Dentistry, Federal University of Santa Catarina, 88040-900 Florianopolis, SC, Brazil
Department of Pathology, Federal University of Santa Catarina, 88040-900 Florianopolis, SC, Brazil
3
Stomatology Clinic, University Hospital, Federal University of Santa Catarina, 88040-900 Florianopolis, SC, Brazil
4
Hematology Service, University Hospital, Federal University of Santa Catarina, 88040-900 Florianopolis, SC, Brazil
5
Department of Dentistry, Federal University of Santa Catarina, 88040-900 Florianopolis, SC, Brazil
6
Integrated Multidisciplinary Health, Federal University of Santa Catarina, 88040-900 Florianopolis, SC, Brazil
2

Correspondence should be addressed to Maria Ines Meurer; meurer.m.i@ufsc.br


Received 2 October 2014; Revised 23 December 2014; Accepted 11 January 2015
Academic Editor: Bruce C. Baguley
Copyright 2015 Caroline Zimmermann et al. This is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
cited.
Dental treatment of patients with leukemia should be planned on the basis of antineoplastic therapy which can be chemotherapy
with or without radiotherapy and bone marrow transplantation. Many are the oral manifestations presented by these patients,
arising from leukemia and/or treatment. In addition, performing dental procedures at different stages of treatment (before, during,
or after) must follow certain protocols in relation to the haematological indices of patients, aimed at maintaining health and
contributing to the effectiveness of the results of antineoplastic therapy. Through a literature review, the purpose of this study
was to report the hematological abnormalities present in patients with leukemia, trying to correlate them with the feasibility of
dental treatment at different stages of the disease. It is concluded in this paper that dental treatment in relation to haematological
indices presented by patients with leukemia must follow certain protocols, mainly related to neutrophil and platelet counts, and the
presence of the dentist in a multidisciplinary team is required for the health care of this patient.

1. Introduction
The insertion of dentistry in the multidisciplinary context
of hematology-oncology is an important part of the success
of cancer treatment. Oral complications can compromise
the protocols of chemotherapy, possibly making it necessary
to decrease the administered dose, the change in treatment
protocol, or even discontinuation of antineoplastic therapy,
directly affecting patient survival [1, 2].
The feasibility to perform certain dental procedures in
leukemia patients depends on the overall state of health
of the patient, as well as the stage of the disease and/or
antineoplastic therapy or hematopoietic stem cell transplantation. Despite the expectation of finding a vast literature
on the leukemia/dental relationship, the bibliographic survey
conducted (PubMed, BIREME, Journals Portal CAPES, and
SciELO) resulted in a few articles involving the amplitude of

this relationship. Facing the need to establish protocols for


the dental care of oncohematological patients at University
Hospital, Federal University of Santa Catarina, a simplified
guide for the guidance of residents in dentistry in the evaluation and treatment of these patients was developed. The guide
consists of tables correlating phases of chemotherapy and
hematopoietic stem cell transplantation to the most common
dental procedures (classification adapted from Sonis et al.
[3]).

2. General Considerations regarding Leukemia


Leukemia is a malignant disease of the blood, where the
uncontrolled proliferation of immature blood cells that originate from hematopoietic stem cell mutation occurs. Eventually these aberrant cells compete with normal cells for space in
the bone marrow, causing bone marrow failure and death [4].

Journal of Oncology

2.1. Classification. The most common leukemias are generally


classified as (1) acute lymphocytic, (2) acute myeloid, (3)
chronic lymphocytic, and (4) chronic myeloid. The classification criteria of leukemia is histological and is based on (a)
the similarity between the leukemic cells and normal cells
(myeloid versus lymphoid) and (b) the clinical course of the
disease (acute versus chronic) [4].
The acute forms of leukemia result from the accumulation
of immature and functionless cells in the bone marrow, with
rapid progression [5], rapidly fatal in untreated patients [6].
Chronic leukemias, in turn, begin slow with uncontrolled
proliferation of more mature and differentiated cells [5].
2.2. Treatment. The treatment of leukemia depends on factors such as type and subtype of the disease, risk factors, and age of the patient. In general, the recommended
treatment is chemotherapy with or without adjuvant treatments. Hematopoietic stem cell transplantation (HSCT) is
performed, in general, in the acute forms of the disease and
some cases of chronic myeloid leukemia:
(i) acute lymphoblastic leukemia (ALL): prophase (initial reduction of leukemic cells), induction (achieve
complete remission), consolidation (increase the
quality of remission), intensification (postremission
further reduction), and maintenance therapy (maintenance of consolidation); prophylactic central nervous system (CNS) therapeutic irradiation or irradiation if CNS is involved; the HSCT can be done in some
cases [7];
(ii) acute myeloid leukemia (AML): induction (until
complete remission), consolidation, and intensification [8];
(iii) chronic myeloid leukemia (CML): remission of leukemic cells and Philadelphia chromosome-positive with
high doses of chemotherapy, monitoring of therapy,
and HSCT [9];
(iv) chronic lymphocytic leukemia (CLL): conventional
treatment is not curative; chemotherapy is performed
as a control [10].
2.2.1. Special Considerations about HSCT. Treatment with
HSCT aims to repopulate the marrow, previously destroyed
with high doses of chemotherapy with or without radiation,
for normal healthy cells. The HSCT can be of the autologous
type (patients own hematopoietic stem cells) or allogeneic
(hematopoietic cells obtained from a donor) [4, 11] and consists of five phases: (1) preconditioning, (2) neutropenic phase
conditioning, (3) engraftment to hematopoietic recovery, (4)
immune reconstitution/recovery from systemic toxicity, and
(5) long-term survival [1].
The main complications of HSCT are graft rejection (for
failure in the patients immunosuppression) and the graftversus-host disease (GVHD), where immunocompetent
donor cells attack the patients antigens, which may lead to
the depletion of T lymphocytes. Potentially fatal, GVHD can
occur soon after HSCT (acute GVHD) or after a few months

(chronic GVHD or cGVHD). With deep and long immunosuppression, the patient becomes susceptible to fungal and
viral infections [4].
2.3. Oral Manifestations of Leukemia. In acute leukemias,
gingival hyperplasia is generally observed, localized or
generalized, mainly affecting the interdental papillae and
the marginal gingiva caused by inflammation, or leukemic
infiltration, and may be localized or generalized, the latter being the most frequent form [3, 5]. The infiltration
of leukemic cells may also involve periapical tissues and
simulate, both clinically and radiographically, periapical
inflammatory lesions [6]. In chronic leukemia, the leukemic
infiltrates in oral tissues is less frequent and can be observed:
pallor of the mucosa, soft tissue infections, and generalized
lymphadenopathy [5].
The manifestations of thrombocytopenia are more common when the platelet count is below 50,000 cells/mm3 [12]
and may manifest as bruising, petechiae in the hard and soft
palate, and also spontaneous gingival bleeding, especially if
the platelet count is below 20,000 cells/mm3 [6].
Opportunistic infections with Candida albicans and Herpes viruses are common and can involve any area of the
mucosa. Ulcers can also result from impaired immune
defense in combating normal microbial flora [6].
2.4. Oral Manifestations Related to HSCT. The most common
oral manifestations related to pre-, immediate post-, and late
post-HSCT are summarized in Table 6.
The oral manifestations that may be present are correlated with the phases of HSCT [1]: (1) preconditioning:
oral infections, ulceration, bleeding, and temporomandibular joint dysfunction; (2) neutropenic phase conditioning:
mucositis, dysgeusia, xerostomia, bleeding, oral pain, opportunistic infections, neurotoxicity, and temporomandibular
dysfunction, usually manifesting with high prevalence and
severe forms; at this stage, the patient may develop hyperacute GVHD with further severe oral complications; (3)
engraftment to hematopoietic recovery: opportunistic infections are common and acute GVHD becomes a concern;
bleeding may be present, xerostomia, neurotoxicity, granulomas/papillomas, and temporomandibular dysfunction;
(4) immune reconstitution/recovery from systemic toxicity:
salivary dysfunction, late viral infections, craniofacial growth
abnormalities, cGVHD, and squamous cell carcinoma; and
(5) the long-term survival: in pediatric patients, particularly
children under 6 years, one can observe complications in the
development of bones and teeth; at this stage, recurrence and
malignant neoplasms can be observed.
In the occurrence of GVHD, mucositis, gingivitis, erythema, and pain are usually observed. In cGVHD, the most
common oral manifestations are lichen-type features, hyperkeratotic plaques, mucocele, atrophic mucosa, ulceration [13,
14], fibrosis with limited mouth opening, hyposalivation, and
xerostomia [1316]. In addition, secondary to cGVHD, the
patients have a greater tendency to develop malignancies
[14, 17, 18].

Journal of Oncology

3. General Considerations regarding


Dental Treatment
The dental management of patients with leukemia is necessarily embedded in a multidisciplinary context, because the
medical complexity that this patient presents may interfere
in the determination of priorities and the time available for
dental treatment. For the US National Cancer Institute [2],
the multidisciplinary team should have oncologists, nurses,
dentists (general and stomatological practitioners), social
workers, nutritionists, and other health professionals, which
may contribute to the prevention and treatment of oral
complications in these patients.
Sonis et al. [3] proposed the classification of patients
into categories of high, moderate, and low risk for dental
treatment, based on the type of leukemia (acute or chronic)
and chemotherapy. Patients at high-risk are those with active
leukemia, which have a high number of neoplastic cells in
the bone marrow and peripheral blood; because of this,
they are thrombocytopenic and neutropenic. This risk group
also includes antileukemic patients under treatment, and
as a result of therapy, present bone marrow suppression.
Considered moderate risk patients are those who successfully
completed the first phase of treatment (induction) and are
undergoing the maintenance phase, thus not showing signs
of malignancy in the bone marrow or peripheral blood;
however, they present myelosuppression due to chemotherapy. In the low-risk category are patients who successfully
completed treatment and present no evidence of malignancy
or myelosuppression.
Basic health care should be part of the patients routine
during antineoplastic therapy and HSCT for maintaining
good oral health and reducing the risk of systemic infections
of oral origin. The objectives of care include prevention
of infection, pain control, maintenance of oral functions,
and management of complications of antineoplastic therapy,
aimed at improving the quality of life of patients [19].
Little et al. [5] and Elad et al. [19] reinforce that the role
of the dentist should occur at three different moments:
(1) pre-antineoplastic treatment evaluation and preparation of patients for this,
(2) guidelines and oral health care during treatment,
(3) posttreatment care.
3.1. Pre-Antineoplastic Treatment Assessment and Patient
Preparation. Dental treatment at this stage is based on priorities and should be directed to the acute needs; elective treatment can be postponed to a time when the patient is appropriate for clinical and laboratory conditions [1, 2, 5, 19, 20].
The dental examination, if possible, should occur immediately after diagnosis and before initiation of chemotherapy
so as to permit the removal of sources of infection of dental
origin [3, 5, 20, 21], since expected neutropenia during
chemotherapy predisposes patients to the spread of infection
[5].

3
The objectives of the pre-antineoplastic treatment dental
evaluation are as follows [1, 3, 5, 2022]:
(1) identify and eliminate sources of existing or potential
infection, without, however, promoting complications or delaying cancer therapy;
(2) educate the patient (or their relatives) about the
importance of maintaining oral health in reducing
problems and oral discomfort before, during, and
after cancer treatment;
(3) warn about the possible effects of antineoplastic
therapy in the oral cavity, such as mucositis;
(4) identify specific issues of the diagnosis of leukemia,
such as leukemic infiltrates in oral tissues.
Injury prevention and oral infections is the focus of dental
treatment in leukemic patients and the care with oral hygiene
(brushing, use of fluoride, and noncariogenic diet) should be
emphasized throughout treatment [1, 5, 19].
Data from the US National Cancer Institute [2] allege
that some cancer centers encourage tooth brushing and
flossing, while others indicate the interruption of brushing
and flossing when blood components have a drop below
specified limits (e.g., platelets <30,000 cells/mm3 ). However,
according to the institute itself, there is no evidence in the
literature regarding the best approach. The centers providing
strategy argue that the benefits of proper brushing and
proper flossing outweigh the risks, because the interruption
of routine oral hygiene increases the risk of infection, and
this could promote bleeding as well as increase the risk of
local and systemic infection. Elad et al. [23] agreed that
dental treatment prior to HSCT is preferred to no dental
intervention.
3.2. Oral Health Care during Antineoplastic Treatment.
Patients undergoing chemotherapy have become immunosuppressed and therefore susceptible to systemic infections.
They are classified as high-risk patients, not only by the
possibility of developing infection, but the extent and severity
of this potential, which can have quick course and be
potentially fatal [24].
The objectives of dental care during chemotherapy are as
follows [1]:
(1) maintain optimal oral health;
(2) treat side effects of antineoplastic therapy;
(3) reinforce to the patient the importance of oral
health in reducing problems/discomforts arising from
chemotherapy.
Apart from oral mucositis, the main oral complication
of chemotherapy, other changes may occur, such as bleeding, increased rates of caries, infections (bacterial, viral,
or fungal), gingival abscesses, recurrent herpetic stomatitis,
candidiasis, salivary gland dysfunction, xerostomia, dysgeusia, and pain [2, 3, 20, 24]. It is important to realize
that infections in the oral cavity can progress to systemic
infections, worsening the health status of the patient, and the
presence of a dentist and/or stomatologist provides important
support to the medical staff [2, 3, 21, 25, 26].

Journal of Oncology

3.3. Post-Antineoplastic Treatment Oral Health Care. In the


post-antineoplastic treatment phase, patients are considered
cured of leukemia and not having oral manifestations due
to illness or chemotherapy, with the exception of those
with sequelae of radiotherapy or children who received
chemotherapy in the stage of tooth formation [3], which may
present hypoplastic areas on tooth enamel (mineralization
disorder) and changes in the development of dental roots
(which are presented short and V-shaped) [27].

was observed among authors regarding the amounts considered minimal for invasive dental procedures in the pre- and
transchemotherapy phases. Tables 1 and 2 show the variation
as well as meeting the recommendations regarding the need
for transfusions, antibiotic prophylaxis, and postponement of
dental treatment [13, 5, 22, 3234].
These explained variations will be presented and discussed in Tables 3, 4, and 5, constructed for each phase of
treatment.

3.4. Special Considerations about Oral Health in HSCT


Patients. Considerations regarding the oral health in HSCT
patients in pre-, immediate post-, and late post-HSCT are
summarized in Table 6.
The principles of dental care before HSCT are very similar
to those discussed in Section 3.1 and must consider the following features: (1) In HSCT, the total dose of chemotherapy
and/or irradiation of the body is performed a few days before
transplantation and (2) immunosuppression will be long
term after transplantation [1].
Even though common oral diseases such as periodontal
disease can impact systemically in HSCT patients, the preHSCT assessment by a dentist is needed, and should include
maintenance of the oral health guidelines.
All patients undergoing HSCT should receive specific
care, particularly those who develop cGVHD. A complete
dental evaluation should occur regularly, and special attention should be focused on early detection of oral cancer and
precursor lesions [14, 17, 18, 28]; diagnosis and treatment of
mucosal lesions [14, 28] and erythema or lichen-type features
with symptomatology [18]; caries prevention [14, 28, 29];
reestablishment of oral health in case of rampant caries
[14, 30], with the possibility of use of fluoride applications
[14] or silver diamine fluoride for disease control and relief
of hypersensitivity [30]; and pharmacological treatment [14,
28, 31] or nonpharmacological treatment [14, 28, 29] of
hyposalivation and xerostomia.
The diagnosis of oral cGVHD depends on the patients
history, clinical findings, and early signs and symptoms [14]
and it is generally not necessary to perform a biopsy [28].
Even after immunosuppressive therapy, patients who
develop cGVHD require long term intensive care. In the
care are the reduction of symptoms, resolution of painful
injuries, and prevention and management of secondary
complications, as well as guidelines for the maintenance of
good oral hygiene [14].

4.1. Dental Treatment in the Prechemotherapy Phase. Table 3


(prechemotherapy) summarizes the dental procedures and
their limitations in the literature, concerning hematological
indices and necessary precedence for the procedure considering the initiation of chemotherapy.
Initially, dental treatment should be directed to the acute
needs [5]. Elective treatments should be postponed to an
opportune time when the patient is in good clinical and
hematological conditions [1, 2, 19, 20].
The US National Cancer Institute [2] argues that interventions at this stage should be directed to the treatment of
lesions in the oral mucosa, carious and endodontic lesions,
periodontal disease, poorly fitting dentures, orthodontic
appliances, temporomandibular joint changes, and salivary
dysfunction.
Elad et al. [19] recommend that the dentist should
eliminate potential sources of trauma in the mucosa, such
as orthodontic appliances, ill-fitting dentures, unsatisfactory
restorations, traumatized teeth, and dental calculus. They also
claim that nonrestorable teeth (with root exposure, severe
periodontal involvement and impacted with pericoronitis
signals) must be extracted. In the case of restorable teeth,
it should be determined if there is enough time for proper
treatment. Multiple extractions should be considered if teeth
are neglected by the patient.
According to Sonis et al. [3], decayed teeth should be
restored when there is no risk of pulpal involvement; if this
risk exists, they should be removed or treated endodontically.
They also state that any tooth with questionable prognosis
should be removed, as well as teeth with periodontal involvement and partially erupted third molars which may prove to
be the foci of pericoronitis.
The American Academy of Pediatric Dentistry [1] argues
that when all dental needs cannot be addressed before the
start of cancer therapy, priority should be eliminating sources
of infection and trauma, as well as extractions and periodontal care. Endodontic treatment of symptomatic nonvital teeth
should be done at least a week before the start of chemotherapy in order to have sufficient time to evaluate the success of
treatment; if this is not possible, extraction is indicated. Teeth
that cannot receive endodontic treatment in one session also
have extraction as a treatment of choice, with antibiotic
prophylaxis (penicillin or clindamycin) for about a week. In
asymptomatic teeth, endodontic treatment should be delayed
until the haematological indices of the patient stabilize (this
includes endodontically treated teeth with periapical lesions,
without signs and symptoms of infection). Teeth unable to
be restored with periodontal pockets greater than 6 mm, with
acute symptomatic infection, significant bone loss, furcation

4. Dental Procedures in Different Stages of


the Disease and Treatment
Dental treatment should be planned according to the antineoplastic therapy [3] and HSCT [19]. The execution of some
dental proceduresespecially those of invasive character
depends on the overall health status of the patient and stage of
antineoplastic treatment in which it lies. Considering the risk
of bleeding and serious infections associated with invasive
procedures in the oral cavity, there are already some protocols
that emphasize the importance of evaluating certain hematological indices, mainly neutrophils and platelets. Variation

Journal of Oncology

Table 1: Minimum haematological values for performance of invasive dental procedures in prechemotherapy treatment patients according
to different authors.
Authors
Eversole et al., 2001 [33]
Little et al., 2007 [5]

Platelet count
<50,000 cell/mm3 : not perform dental or
periodontal surgery in office setting.
<50,000 cell/mm3 : avoid invasive procedures.
<40,000 cell/mm3 : perform transfusions in invasive
procedures.

>75,000 cell/mm3 : without additional support.


40,000 to 75,000 cell/mm3 : Platelet transfusion may
be considered in the preoperative and postoperative
(24 hours).
<40,000 cell/mm3 : Postpone the dental treatment.
American Academy of
In the case of dental emergency, contact the patients
Pediatric Dentistry, 2013 [1]
physician before dental treatment to discuss
supportive measures, such as platelet transfusion,
control of bleeding, and need for hospitalization.
Other coagulation tests may be necessary in some
cases.

US National Cancer
Institute, 2011 [2]

>60,000 cell/mm3 : without additional support.


30,000 to 60,000 cell/mm3 : optional transfusion
for noninvasive procedure.
<30,000 cell/mm3 : Platelets should be transfused 1 h
before the procedure. Obtain immediate
postinfusion platelet count; transfuse regularly to
maintain counts >30,00040,000 cell/mm3 until the
start of healing.

Neutrophil count

<500 cell/mm3 : antimicrobial prophylaxis (or with


leukocytes <2,000 cells/mm3 ).
>1,000 cell/mm3 : no need for antibiotic prophylaxis.
Some authors suggest that prophylaxis is performed
with values between 1,000 and 2,000cell/mm3
(following recommendations of the American Heart
Association). If infection is present or there is doubt,
more aggressive antibiotic prophylaxis may be
indicated and should be discussed with the medical
team.
<1,000 cell/mm3 : Postpone the dental treatment. In
cases of emergency, discuss antibiotic coverage and
endocarditis prophylaxis before treatment with the
medical team. Hospitalization may be required.
>2,000 cell/mm3 : without the need for antibiotic
prophylaxis.
1,000 to 2,000 cell/mm3 : antibiotic prophylaxis (low
risk).
<1,000 cell/mm3 : antibiotic prophylaxis with
Amikacin 150 mg/m2 1 h before surgery and
Ticarcillin 75 mg/Kg IV 1 h before surgery. Repeat
both 6 h postoperative.

Table 2: Minimum hematological values for performing invasive dental procedures in patients undergoing chemotherapy, according to
different authors.
Authors
Sonis et al., 1995 [3]
Haytac et al., 2004 [32]
Brennan et al., 2008 [22]
Koulocheris et al., 2009
[34]

Platelet count
<100,000 cell/mm3 : elective dental treatment should
be postponed.
<40,000 cell/mm3 : periodontal probing and dental
extractions contraindicated.
<50,000 cell/mm3 : contraindication to perform
invasive procedures.

Neutrophil count
<3,500 cell/mm3 (leukocytes): elective dental
treatment should be postponed.
<1,500 cell/mm3 : periodontal probing and dental
extractions contraindicated.
<1,000 cell/mm3 : contraindication to perform
invasive procedures.

>60,000 cell/mm3 : acceptable for oral surgery.

>1,000 cell/mm3 : acceptable for oral surgery.

exposure, mobility, and impacted and residual roots should


be removed. Ideally, extraction should occur two weeks
before the start of the antineoplastic treatment or at least
7 to 10 days before. Finally, the academy recommends that
surgical procedures should be as atraumatic as possible,
without leaving remnant bone edges and with satisfactory
suture of the wound. If there is infection associated with the
tooth, antibiotic prophylaxis should be done for a week and
by the drug ideally chosen by antibiogram.
According to Little et al. [5], the extraction should be
made, preferably three weeks prior to chemotherapy or
radiotherapy and at least 10 to 14 days earlier. If the platelet
count is less than 50,000 cells/mm3 , invasive procedures
should be avoided; when less than 40,000 cells/mm3 , this
indicates performing transfusions. Antimicrobial prophylaxis is recommended when the leukocytes count is less than

2,000 cells/mm3 or less than 500 cells/mm3 . Partially erupted


molars can be a source of infection due to pericoronitis.
If the gingival tissue which partially covers the tooth is a
potential factor for infection, the tissue should be excised, if
the hematological levels permit.
Toljanic et al. [35] conducted a prospective study aimed at
assessing a minimum protocol for prechemotherapy dental
treatment involving 48 patients with solid or hematological
neoplasms, empirically classifying the chronic changes of
odontogenic origin as mild, moderate, or severe, considering the probability of them developing into acute processes during chemotherapy. In acute diagnosed alterations
based on signs (edema, purulent drainage, and compatible radiographic changes) and symptoms (pain, tenderness,
and fever), the source of infection was removed before
chemotherapy. In contrast, in chronic changes, the source

Journal of Oncology

Table 3: Possibility of dental procedures in the prechemotherapy phase.


Procedure
Type I
Exam
Clinical
Radiographic
Hygiene instructions
Molding
Type II
Simple restorations (ART)
Prophylaxis and supragingival scaling

Considerations and restrictions

Time before the


start of CT

No restrictions.

Elective procedure, postpone

No restrictions.

Elective treatment, postpone.


Consider removing orthodontic appliances.

More complex restorations

Solely for adequacy of the oral environment.


Consider use of provisional restorative materials (e.g., glass ionomer).

Scaling and root planning


(subgingival)

Invasive procedure of high-risk carried out carefully. To evaluate


hematological indices of platelets and neutrophils.
Need for antibiotic prophylaxis.

Orthodontics
Type III

Endodontics
Symptomatic tooth

Evaluate hematological indices of platelets and neutrophils.


Need for antibiotic prophylaxis.
Consider extraction if endodontics fail.

At least 1 week [1]

Asymptomatic tooth

Postpone (tricresol formalin)


OR
Evaluate hematological indices of platelets and neutrophils. Need for
antibiotic prophylaxis.

At least 1 week [1]

Simple extractions

Invasive procedure of high-risk.


Evaluate hematological indices of platelets and neutrophils. Need for
antibiotic prophylaxis.

3 weeks; minimum
1014 days [5]
2 weeks; minimum
710 days [1]

Curettage (gingivoplasty)

Elective procedure, invasive and high-risk.


Postpone.

Type IV

Type V
Multiple extractions
Flap surgery/gingivectomy
Extraction of impacted tooth
Apicoectomy
Single implant placement
Type VI

If for adequacy of the oral environment, evaluate hematological


indices of platelets and neutrophils.
Need for antibiotic prophylaxis.
If elective, postpone.
Elective procedure, invasive and high-risk.
Postpone.

Extraction of an entire arch or both

If adequacy of the oral environment, evaluate hematological indices


of platelets and neutrophils.
Need for antibiotic prophylaxis.
If elective, postpone.

Extraction of multiple impacted teeth


Flap surgery
Orthognathic surgery
Placement of multiple implants

Elective procedure, invasive and high-risk.


Postpone.

3 weeks; minimum
1014 days [5]
2 weeks; minimum
710 days [1]

3 weeks; minimum
1014 days [5]
2 weeks; minimum
710 days [1]

Journal of Oncology

Table 4: Possibility of dental procedures in transchemotherapy phase.


Procedure
Type I
Exam
Clinical
Radiographic
Hygiene instructions
Molding
Type II
Simple restorations (ART)
Prophylaxis and supragingival scaling

Considerations or restrictions

Time between
cycles

No restrictions.

Elective procedure. Postpone.

No restrictions.

Elective treatment.
Consider removing orthodontic appliances.

More complex restorations

Solely for adequacy of the oral environment.


Consider use of provisional restorative materials (eg., Glass ionomer).

Scaling and root planning


(subgingival)

Invasive treatment, of high-risk, perform carefully. Evaluate


hematological indices of platelets and neutrophils.
Need for antibiotic prophylaxis.

Symptomatic tooth

Evaluate hematological indices of platelets and neutrophils.


Need for antibiotic prophylaxis.
Consider extraction if endodontics fails.

At least 1 week [1]

Asymptomatic tooth

Postpone (tricresol formalin).


OR
Evaluate hematological indices of platelets and neutrophils.
Need for antibiotic prophylaxis.

At least 1 week [1]

Orthodontics
Type III

Endodontics

Type IV
Simple extractions
Curettage (gingivoplasty)
Type V
Multiple extractions
Flap surgery/gingivectomy
Extraction of impacted tooth
Apicoectomy
Single implant placement
Type VI

Elective treatment, invasive and high-risk. Postpone.

3 weeks; minimum
1014 days [5]
2 weeks; minimum
710 days [1]

If adequacy of the oral environment, evaluate hematological indices


of platelets and neutrophils.
Need for antibiotic prophylaxis.
If elective, postpone.

3 weeks; minimum
1014 days [5]
2 weeks; minimum
710 days [1]

Invasive treatment of high-risk. Evaluate hematological indices of


platelets and neutrophils.
Need for antibiotic prophylaxis.

Elective procedure, invasive and high-risk.


Postpone.

Extraction of an entire arch or both

If adequacy of the oral environment, evaluate hematological indices


of platelets and neutrophils.
Need for antibiotic prophylaxis.
If elective, postpone.

Extraction of multiple impacted teeth


Flap surgery
Orthognathic surgery
Placement of multiple implants

Elective procedure, invasive and high-risk.


Postpone.

3 weeks; minimum
1014 days [5]
2 weeks; minimum
710 days [1]

Journal of Oncology
Table 5: Possibility of dental procedures in postchemotherapy phase.

Intervention in postchemotherapy
Type I
Exam
Clinic
Radiographic
Hygiene instructions
Molding
Type II
Simple restorations (ART)

Considerations and restrictions

No restrictions.

No restrictions.

Prophylaxis and supragingival cell scaling


Orthodontics
Type III
More complex restorations
Scaling and root planning cell (subgingival)
Endodontics
Symptomatic tooth
Asymptomatic tooth
Type IV
Simple extractions
Curettage (gingivoplasty)
Type V
Multiple extractions
Flap surgery/gingivectomy
Extraction of impacted tooth
Apicoectomy
Single implant placement
Type VI
Extraction of an entire arch or both
Extraction of multiple impacted cell teeth
Flap surgery
Orthognathic surgery
Placement of multiple implants

Completed chemotherapy and after two years free of disease, one can restart the
orthodontic treatment

No restrictions.

Need for antibiotic prophylaxis until six months after completion of chemotherapy.

Need for antibiotic prophylaxis until six months after completion of chemotherapy.

Need for antibiotic prophylaxis until six months after completion of chemotherapy.

of infection was not removed. Chronic lesions of odontogenic origin were identified in 79% of patients, where 44%
were considered serious chronic illness; of these, only 4%
had episodes of fever diagnosed as odontogenic in origin,
which were treated with antibiotics without interruption of
chemotherapy. For the authors, these results demonstrated
that patients with chronic odontogenic lesions can safely
undergo chemotherapy without dental procedures, since
the conversion of chronic processes in acute cases was
uncommon and when sharpening occurred it was effectively
treated without interruption of therapy and without adversely
affecting the oncological treatment. This strategy would
significantly change the established protocols, which recommend a more aggressive prechemotherapy dental treatment.
The authors reasoned that, depending on the severity of the
cancer, there may be a need to quickly start chemotherapy to
maximize its therapeutic effects and in that narrow window of
time, the extraction of teeth without potential recovery may

be the only viable treatment option and still the possibility


of infection after tooth extraction would delay the repair of
the wound. It is concluded that the treatment of chronic
odontogenic lesions can be safely postponed until the end of
chemotherapy, considering the therapeutic benefits.
According to Haytac et al. [32] a neutrophil count of
1,500/mm3 and platelets of 40,000 cells/mm3 are required for
performing periodontal probing or extractions. The procedures must be performed under antibiotic cover and at least
three days before the start of chemotherapy (approximately 10
days before the granulocyte count falls below 500 cells/mm3 );
when not possible, dental treatment should be postponed
until the haematological indices increase.
The American Academy of Pediatric Dentistry [1] argues
that orthodontic appliances should be removed if the patient
has deficient oral hygiene and/or in cases where the protocol
of antineoplastic treatment confers risk for developing moderate or severe oral mucositis; simple devices that do not

(i) Maintain and reinforce the importance of optimal


oral health.
(ii) Treat side effects of HSCT therapy.
(iii) Pay attention to periodontitis and gingivitis as
potential sources of bacteremia.
Neutropenic conditioning phase
(i) Dental procedures should not be performed at
this stage
(ii) If emergencies, perform the necessary dental
approach, with the participation of medical staff.
Engraftment to hematopoietic recovery
(i) Monitoring and management of oral
complications of HSCT
(ii) Invasive procedures only with the approval of the
medical team
(iii) Strengthening the maintenance guidelines of
good oral hygiene and noncariogenic diet
(iv) Special attention to xerostomia and GVHD.

Pre-HSCT
(preconditioning)

(i) Oral infections


(ii) Soreness
(iii) Bleeding
(iv) Temporomandibular dysfunction.

(i) Identify and eliminate sources of existing


or potential infection.
(ii) Orientate the patient about the
importance of maintaining oral health.
(iii) Warn about the possible effects of
antineoplastic therapy in the oral cavity.

(i) Complete necessary dental treatment


(ii) Elective treatment should be delayed
until the re-establishment of immunity (at
least 100 days after transplant, or more in the
case of oral complications or other cGVHD).

Special
considerations

Oral
manifestations

Oral health

Dental
treatment

Immediate post-HSCT
(neutropenic conditioning phase and engraftment to
hematopoietic recovery)
(i) Mucositis
(ii) Dysgeusia
(iii) Xerostomia
(iv) Hemorrhage
(v) Oral pain
(vi) Opportunistic infections
(vii) Neurotoxicity
(viii) Temporomandibular dysfunction
(ix) Acute GVHD.

(i) Diagnosis and treatment of mucosal lesions and


lichen-type features with symptoms
(ii) Caries prevention and reestablishment of oral
health in case of rampant caries
(iii) Treatment of hyposalivation and xerostomia
(iv) Early detection of oral cancer and precursor lesions.
Immune reconstitution/recovery from systemic toxicity
(i) Periodic dental evaluation
(ii) Avoid invasive procedures
(iii) Clarify risks and benefits of orthodontic appliances.
Long-term survival
(i) Periodic dental evaluation
(ii) In the first 12 months after HSCT:
(a) avoid routine dental care, including scaling and
periodontal planning;
(b) if emergencies, strategies to reduce inhalation of
aerosols and antibiotic prophylaxis;
(c) before invasive procedures, consider the use of IgG,
antibiotics, corticosteroids, and/or platelet transfusion.

(i) Chronic GVHD


(ii) Late viral infections
(iii) Salivary dysfunction
(iv) Squamous cell carcinoma
(v) Craniofacial growth abnormalities (children)
(vi) Impairment of bones and teeth (children).

Late post-HCST
(immune reconstitution/recovery from systemic
toxicity and long-term survival)

Table 6: Special considerations regarding oral complications, oral health, and dental treatment in pre-, immediate post-, and late post-HSCT.

Journal of Oncology
9

10
irritate the soft tissues, removable appliances, or retainers
well adapted may be maintained provided that the patient
has good oral hygiene. Sheller and Williams [36] defend that
orthodontic appliances should be removed.
It is important that the dentist is aware of the signs and
symptoms of periodontal disease, since these can be subtle
when the patient is immunosuppressed [1, 37].
After treatment of acute needs, other procedures such
as smoothing of rough restorations, rounding, or restoration
of tooth fractures may be performed, in addition to the
assessment of dentures. Scaling procedures and root planning
should be performed to prevent periodontal infections, as
well as enhancing oral hygiene instruction and the use of
mouthwash with fluoride in preventing dental caries [3, 5].
4.2. Dental Treatment in the Transchemotherapy Phase.
Table 4 refers to the stage where the patient is undergoing
chemotherapy and lists the dental procedures and restrictions
assigned to it, referring to haematological indices and considering the period between cycles of chemotherapy.
In high-risk patients (active or under leukemia bone
marrow suppression) dental intervention is limited to emergency care. However, oral hygiene must be maintained by the
use of mouthwashes and mild antimicrobial and antiseptic
solutions, in order to promote ulcer healing and minimize
complications from infection. When there is evidence of oral
infection, high-risk patients should receive broad-spectrum
antibiotics intravenously [3, 5]. In UH/UFSC 0.12%, solutionbased nonalcoholic chlorhexidine gluconate is used in the
form of daily mouthwash or applied with gauze or swab.
In patients at moderate risk (maintenance phase), the
myelosuppression peak is most evident, usually after 14 days
of drug administration, and at this time, dental treatment
should be avoided; before or 21 days after the start of
chemotherapy the treatment can be performed; however,
the doctor should be consulted. If the leucocyte count is
below 3,500 cells/mm3 or the platelet count is less than
100,000 cells/mm3 , elective dental treatment should be postponed [3]. According to these authors, type I procedures
can be performed according to standard protocols, since in
types II, III, and IV procedures, antimicrobial prophylaxis is
recommended.
Tong and Rothwell [24] do not recommend routine
antibiotic prophylaxis for dental procedures in patients
undergoing chemotherapy; however, for invasive procedures
such as tooth extractions and other deep periodontal scaling
procedures that can cause significant bleeding and propagation of bacteria into the bloodstream, antibiotic coverage
should be performed.
Koulocheris et al. [34], citing other authors, state that
in oral surgical procedures during chemotherapy, the benefit/risk to the patient must be considered, as well as the consequences of chemotherapy cycles; these procedures should
therefore be planned and agreed on an interdisciplinary level.
Furthermore, the surgical procedure should be the most
conservative possible, with trans and postantibiotic prophylaxis and postoperative platelet transfusion if necessary. It
is claimed, in addition, that an absolute neutrophil count

Journal of Oncology
greater than 1000 cells/mm3 and platelet count of at least
60,000 cells/mm3 are acceptable rates for oral surgeries.
When there is spontaneous bleeding resulting from
minor trauma, the dentist should strive to improve the oral
hygiene of the patient and use local measures to control the
bleeding. If these measures are not sufficient, platelet transfusion may be required [5].
The management for control of oral bleeding includes
the use of vasoconstrictor agents, clots, and tissue guards.
To reduce the flow of blood from bleeding vessels, one can
use epinephrine; to organize and stabilize blood clots, topical
thrombin and/or collagen hemostatic agents can be used;
and to stanch the bleeding sites and protect organized clots,
the application of the mucosa adhesive products, such as
those based on cyanoacrylate, may be performed. The topical
aminocaproic acid can be useful in patients with friable
clots and intravenous administration may be considered,
in some cases, to improve coagulation and the formation
of stable clots [2]. Topical use of tranexamic acid is also
cited as an effective hemostatic in reducing the incidence
of postoperative bleeding in patients taking continuous use
of oral anticoagulants [38, 39]. Coetzee [40] reports the
empirical use of 500 mg crushed tablets ground in moist
cotton at the site of the surgical wound after tooth extraction, or diluted in water for mouthwash, suggesting it as
an option.
4.3. Dental Treatment after Chemotherapy. Table 5 relates the
postchemotherapy period and summarizes the considerations and constraints in the literature for performing dental
procedures.
Patients who were cured of leukemia are considered to
be of low risk and can be met with normal dental treatment
regimens [3]. After completion of cancer therapy and only
after two years free of disease, the orthodontic treatment that
was interrupted can be restarted [36].
Koulocheris et al. [34] suggest that antibiotic prophylaxis
during oral and maxillofacial surgical procedures should be
performed for at least six months after the completion of
chemotherapy.
4.4. Dental Treatment in Different Phases of Chemotherapy
Treatment. Table 7 shows, in summary form, the considerations and limitations related to dental procedures at different
stages of antineoplastic treatment.
Noninvasive procedures do not require additional care
and may be performed at any stage of the disease or
chemotherapy. Fit in this situation the type I (clinical examination, radiographs, and oral hygiene instruction) and type
II procedures (simple restorations, atraumatic restorative
treatmentART, supragingival scaling and prophylaxis) [3].
Since the priority is the treatment of leukemia before the
diagnosis (prechemotherapy phase) or during antineoplastic
treatment, some dental procedures, classified as type I (molding) and type II (orthodontic treatment), are considered
elective for these patients, and even in the postchemotherapy
phase, some restrictions must be considered when related to
orthodontic treatment.

Journal of Oncology
There are procedures, however, that are considered nonsurgical (type III)such as the realization of more complex restorations, scaling, root planning (subgingival), and
endodontic treatmentbut they require special care in the
prechemotherapy and transchemotherapy phases, considering the general state of health and the risk versus benefit to
the patient. Some authors suggest that periodontal procedures such as probing and periodontal scaling could cause
bacteremia [4144]. In addition, the endodontic treatment
protocol for asymptomatic teeth, according to the literature,
is not well established. Thus, the realization of endodontics
has to justify the removal of infectious foci; however, some
professionals prefer, in such situations, to adopt a radical
behavior, performing the extraction of the dental element
in question in order to avoid future complications. In the
postchemotherapy period, these dental procedures can be
performed without restrictions.
Invasive procedures such as simple extractions (type IV),
multiple extractions (type V), or those of an entire arch or
entire mouth (type VI) can be performed, but its execution
is dependent on the patients risk and should therefore the
risk versus the benefit should be considered in specific situations [3]. We believe that gingivoplasty procedures, multiple
extractions (no infectious foci) flap surgery (gingivectomy),
extraction of single or multiple impacted teeth, apicoectomy,
placing implants, and orthognathic surgery are considered
elective treatments before the diagnosis and/or treatment
of leukemia and should not be performed until the patient
completesand maintainstheir antineoplastic treatment
successfully.

11
Table 7: Possibility of dental procedures at various stages of
chemotherapy.
Intervention
Type I
Exam
Clinical
Radiographic
Oral hygiene instruction
Molding
Type II
Simple restorations (ARTs)
Prophylaxis and supragingival
scaling
Orthodontics
Type III
More complex restorations
Scaling and root planning
(subgingival)
Endodontics
Symptomatic teeth
Asymptomatic teeth

Trans

Post

NR
NR
NR
E

NR
NR
NR
E

NR
NR
NR
NR

NR

NR

NR

NR

NR

NR

R
R
HI, AP

R
R
HI, AP

NR

R
HI, AP
E, R
HI, AP

R
HI, AP
E, R
HI, AP

R,
HI, AP
EIHR

R,
HI, AP
EIHR

R,
HI, AP
EIHR
EIHR
EIHR
EIHR

R,
HI, AP
EIHR
EIHR
EIHR
EIHR

R,
HI, AP

R,
HI, AP

EIHR

EIHR

EIHR
EIHR
EIHR

EIHR
EIHR
EIHR

R
R
R

NR

NR
NR

Type IV
Simple extractions
Curettage (gingivoplasty)
Type V
Multiple extractions

4.5. Special Considerations about Dental Treatment in HSCT


Patients. The considerations of the dental treatment in the
pre-, immediate post-, and late post-HSCT are summarized
in Table 6.
The American Academy of Pediatric Dentistry [1] recommends that dental treatment is made dependent on each
phase of HSCT. In the preconditioning phase, all dental
treatment should be completed before the patient becomes
immunosuppressive. Elective treatment should be delayed
until the reestablishment of immunity (at least 100 days after
transplant, or more in the case of oral complications or other
cGVHDs). In the neutropenic conditioning phase, the focus
is the monitoring and management of oral complications,
with reinforcement of maintenance guidelines of good oral
hygiene. Dental procedures should not be performed at this
stage; in the case of emergencies, dental approach should
be developed with the participation of the medical staff. In
the engraftment phase to hematopoietic recovery, a dental
assessment should be performed, with special attention to
xerostomia and GVHD. Invasive procedures should be made
only with the approval of the medical staff; the patient should
be encouraged to maintain good hygiene with a noncariogenic diet. In the immune reconstitution/recovery phase
from systemic toxicity, a periodic evaluation with dental
radiography can be performed; however, invasive procedures
should still be avoided; clarifying the risks and benefits of
the use of orthodontic appliances is recommended. Finally,
in the long-term survival phase, a routine dental evaluation

Pre

Flap surgery/gingivectomy
Extraction of impacted tooth
Apicoectomy
Single implant placement
Type VI
Extraction of an entire arch or both
Extraction of multiple impacted
teeth
Flap surgery
Orthognathic surgery
Placement of multiple implants

R
R
R
R
R
R
R

NR: no restriction, R: with restriction, E: elective, EIHR: elective, invasive,


and high-risk, HI: need for evaluation of hematological indices, and AP:
antibiotic prophylaxis.

with interdisciplinary and multidisciplinary involvement is


necessary.
The authors differ somewhat as to the best approach for a
better dental protocol in HSCT patients, but are unanimous
in stating that the assessment and dental care are needed.
Raber-Durlacher et al. [37] investigated the correlation
between gingivitis/periodontitis and the development of
bacteremia during the period of neutropenia after HSCT.
Eighteen patients were examined and classified into two
groups: (1) periodontally healthy (probing pocket depth: PPD

12
4 mm and bleeding on probing: BOP 10%) and (2) the
presence of gingivitis (PPD 4 mm and BOP > 10%) or
periodontitis (PPD > 4 mm and BOP 10%). Only 28% of
the patients were considered periodontally healthy. Of the
total, 67% of the patients developed bacteremia (diagnosed
by blood samples collected 2 times per week), and group 2
had more frequent episodes during the neutropenia phase
than group 1. The authors suggested that gingivitis and
periodontitis may represent a risk factor for the development of bacteremia, which has also been shown in other
studies [43, 44]. They further stated that the exacerbation of
gingivitis and chronic periodontitis is rare, probably due to
the institution of prophylactic therapy; on the other hand,
common illnesses should not be overlooked, such as potential
underdiagnosed of bacteremia source, particularly during
periods of neutropenia.
Melkos et al. [45] conducted a prospective study of 58
patients undergoing HSCT and evaluated the preexisting
odontogenic lesions, dental care, and the effect of both
on the medical procedure. All patients were referred for a
dental evaluation before the HSCT, being examined by two
experienced dentists through clinical examination (soft and
hard tissues) and radiographic (panoramic and occasionally
for symptomatic periapical teeth). Infectious foci teeth were
considered with periapical and periodontal infection and
those semi-impacted. The type of pretransplant dental work
and the occurrence of posttransplant complications (mucositis, infections, graft versus host disease (GVHD), and relapse
of disease) were evaluated for an average of 50.45 weeks
after the date of transplantation. The protocol for dental
treatment included restoration of active caries and extraction
of nonrestorable teeth and those with advanced periodontal disease; nonvital teeth were endodontically treated or
extracted, whereas periapical lesions were treated endodontically, performing apicoectomy or extraction. Patients were
divided into two groups: (I) no infectious foci or complete
dental treatment before transplantation ( = 36) and (II)
with infectious foci, submitted to transplantation without
dental intervention ( = 22). Posttransplant complications
were observed in 75% of patients in group I and 95.4% in
group II. The impact of infectious outbreaks in the occurrence
of posttransplant infections was not statistically significant,
as well as correlations between decayed, impacted, and
semierupted teeth, fever of unknown origin, mucositis, and
the survival rate of patients with preexisting foci; however,
the infectious foci were significant when associated with
acute GVHD, mainly impacted teeth and periapical lesions.
A higher rate of complications was found in group II,
indicating the importance of evaluation and pretransplant
dental work. It was concluded that dental treatment before
HSCT should not be radical. Restorative and preventative
techniques, however, must be individually adjusted for each
patient.
Yamagata et al. [46] also conducted a prospective study
of 41 patients who were undergoing HSCT using a conservative dental protocol. All patients were evaluated by clinical
examination of the oral soft and hard tissues and, if necessary,
radiographs were requested. Of the 41 patients, 36 required
one or more dental interventions. The following diagnoses

Journal of Oncology
and procedures were performed: 101 carious lesions: 40
were restored and 61 were untreated; 5 pulpitis treated with
endodontics; 10 teeth with apical periodontitis greater than
5 mm and 33 with less than 5 mm: 7 lesions were surgically
removed, 5 teeth were endodontically treated (including two
with symptomatology), and 31 teeth with lesions smaller than
5 mm and asymptomatic received no treatment; 94 teeth with
periodontitis: 6 were extracted and 88 preserved, with survey
monitoring and hygiene education; 21 partially erupted wisdom teeth: 3 presenting symptomatology were removed, the
rest were untreated. All dental procedures were performed up
to 10 days before HSCT, without change interruption or delay
in the planning of the transplant. No patient had signs or
symptoms of odontogenic infection during the immunosuppression period. The authors concluded that the conservative
protocol appeared to be suitable for pre-HSCT patients.
Abdullah and Ahmad [47] conducted a study of 44
pediatric patients. Dental conditions were evaluated by clinical examination before HSCT. In the case of symptomatic
tooth periapical radiographs were performed. Decayed teeth
considered unviable were extracted, and the others were
restored. In patients at high-risk of caries, sealant was applied.
All patients received oral hygiene guidelines. The patients
were evaluated after 1, 3, and 6 months after HSCT. Most
patients (65.9%) needed some type of pre-HSCT dental
treatment, having performed 101 restorations, 13 extractions,
and 19 sealants. Within 6 months of monitoring, 10% of the
patients who did not receive pre-HSCT dental treatment had
odontogenic infection. No cases of odontogenic infection
were observed in patients who previously received dental
care. The authors concluded that the pre-HSCT dental treatment can reduce the occurrence of infection of dental origin,
and it is important to prevent serious infections.
The US National Cancer Institute [48] points out that the
time of reconstitution of the immune system in transplant
patients can range from 6 to 12 months and that the dental
care routine should not be done in this period, including
scaling and periodontal planning. Procedures that produce
aerosol, such as ultrasound equipment and high speed, can
also present a risk of aspiration of debris and bacteria and
cause pneumonia in these patients [19, 48]. If emergency
treatment is required, strategies for reducing aerosol aspiration and antibiotic prophylaxis should be used. Finally, it is
recommended that the use of IgG, antibiotics, corticosteroids,
and/or platelet transfusion should be considered before
implementing invasive procedures [48].

5. Final Considerations
From the literature review conducted, several oral manifestations in leukemic patients arose. These manifestations are
often the first sign of leukemia and may present clinically
as leukemic infiltration in oral tissues as well as simulating
a periapical lesion. Other symptoms may occur such as
pale mucosa, poor wound healing, bleeding (petechiae and
ecchymoses), atypical or recurrent candidiasis, recurrent
herpes infections, and ulcerations in the oral mucosa. During
antineoplastic treatment (chemotherapy, mostly), the main
complication is mucositis.

Journal of Oncology
Other conditions that may also occur include bleeding,
increase the rate of decay, infection, gum abscess, recurrent
herpetic stomatitis, candidiasis, salivary gland dysfunction,
xerostomia, dysgeusia, and pain. In the posttherapy period,
patients are considered cured and usually present no sequelae
of treatment.
Oral manifestations are similar in patients undergoing
HSCT; however, generally these cases are due to long-term
immunosuppression of the patient even after the transplantation. Special features are observed in patients undergoing
allogeneic HSCT, such as cGVHD, which typically manifests
as lichen-type features, hyperkeratotic plaques, mucocele,
and fibrosis with limited mouth opening, and are more likely
to develop malignancies such as squamous cell carcinoma.
Performing dental procedures can offer risk to the patient,
depending on his state of health and phase of therapy.
Furthermore, some procedures offer greater risk than others.
Thus, noninvasive procedures (type I and type II) can be
performed at any stage of the disease or treatment. Type III
procedures may require special care. Finally, invasive procedures (types IV, V, and VI) offer higher risk. In emergency
situations of risk considered, particularly those involving pain
(acute cases), the patient should be assisted, if necessary, in a
hospital setting, with the institution of measures to increase
the hematological indices (transfusions) and, if applicable,
with antibiotic coverage.
In assessing patients for dental procedures, two hematological indices are particularly important: neutrophil and
platelet counts. At low levels of neutrophil counts, and
when the procedure cannot be delayed, prophylactic antibiotic therapy protocols should be considered, being variable
according to the degree of neutropenia; there is no strict
consensus among authors, but most recommended antibiotic
prophylaxis with values less than 1,000 cells/mm3 . In the case
of the platelet count, the authors consider the need for transfusion from indices between 40,000 and 60,000 cells/mm3 .
Thus, we conclude, based on the literature review presented here, that the dental treatment in relation to haematological indices presented by patients with leukemia should
follow some judicious protocols, mainly related to neutrophil
and platelet counts. However, it is noteworthy that many of
these studies are based on expert opinion. The presence of
the dentist in a multidisciplinary team is essential, since we
understand that maintaining oral health contributes significantly to the overall health and improved quality of life for
patients through the use of dental approaches based on scientific evidence, preventive, curative, and palliative in nature.

Conflict of Interests
The authors declare that there is no conflict of interests
regarding the publication of this paper.

References
[1] American Academy of Pediatric Dentistry, Guideline on dental
management of pediatric patients receiving chemotherapy,
hematopoietic cell transplantation, and/or radiation, Journal
of Pediatric Dentistry, vol. 35, no. 5, pp. E185E193, 2013,
http://www.ncbi.nlm.nih.gov/pubmed/24290549.

13
[2] US National Cancer Institute, Oral Complications of Chemotherapy and Head/Neck Radiation, US National Cancer Institute,
2011, http://www.cancer.gov/cancertopics/pdq/supportivecare/
oralcomplications/HealthProfessional.
[3] S. T. Sonis, R. C. Fazio, and L. Fang, Principles and Practice of
Oral Medicine, WB Saunders, 1995.
[4] M. R. Howard and P. J. Hamilton, Leukaemia, in Haematology,
pp. 3366, Elsevier, Philadelphia, Pa, USA, 3rd edition, 2008.
[5] J. W. Little, D. A. Falace, C. S. Miller, and N. L. Rhodus,
Disorders of white blood cells, in Dental Magenement of the
Medically Compromised Patient, pp. 373395, 2007.
[6] B. Neville, D. Damm, C. Allem, and J. Bouquot, Hematologic
disorders, in Oral and Maxillofacial Pathology, pp. 573613,
Elsevier, 3rd edition, 2009.
[7] R. Wasch, W. Digel, and M. Lubbert, Acute lymphoblastic
leukemia (ALL), in Concise Manual of Hematology and Oncology, M. Andreeff, B. Koziner, H. Messner, and N. Thatcher, Eds.,
pp. 400414, Springer, Berlin, Germany, 2008.
[8] K. Heining-Mikesch and M. Lubbert, Acute myeloid leukemia
(AML), in Concise Manual of Hematology and Oncology, M.
Andreeff, B. Koziner, H. Messner, and N. Thatcher, Eds., pp.
415420, Springer, Berlin, Germany, 2008.
[9] W. Lange and C. Waller, Chronic myeloid leukemia (CML),
in Concise Manual of Hematology and Oncology, pp. 432438,
Springer, Berlin, Germany, 2008.
[10] J. Burger and J. Finke, Chronic lymphocytic leukemia (CLL),
in Concise Manual of Hematology and Oncology, pp. 470476,
Springer, Berlin, Germany, 2008.
[11] K. Durey, H. Patterson, and K. Gordon, Dental assessment
prior to stem cell transplant: treatment need and barriers to
care, British Dental Journal, vol. 206, no. 9, article E19, 2009.
[12] J. B. Epstein, L. Vickars, J. Spinelli, and D. Reece, Efficacy
of chlorhexidine and nystatin rinses in prevention of oral
complications in leukemia and bone marrow transplantation,
Oral Surgery Oral Medicine and Oral Pathology, vol. 73, no. 6,
pp. 682689, 1992.
[13] A. H. Filipovich, D. Weisdorf, S. Pavletic et al., National Institutes of Health consensus development project on criteria for
clinical trials in chronic graft-versus-host disease: I. Diagnosis
and staging working group report, Biology of Blood and Marrow
Transplantation, vol. 11, no. 12, pp. 945956, 2005.
[14] N. Treister, C. Duncan, C. Cutler, and L. Lehmann, How we
treat oral chronic graft-versus-host disease, Blood, vol. 120, no.
17, pp. 34073418, 2012.
[15] K. M. Hull, I. Kerridge, and M. Schifter, Long-term oral
complications of allogeneic haematopoietic SCT, Bone Marrow
Transplantation, vol. 47, no. 2, pp. 265270, 2012.
[16] H. S. Brand, C. P. Bots, and J. E. Raber-Durlacher, Xerostomia
and chronic oral complications among patients treated with
haematopoietic stem cell transplantation, British Dental Journal, vol. 207, no. 9, article E17, 2009.
[17] R. A. Abdelsayed, T. Sumner, C. M. Allen, A. Treadway, G. M.
Ness, and S. L. Penza, Oral precancerous and malignant lesions
associated with graft-versus-host disease: report of 2 cases,
Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and
Endodontology, vol. 93, no. 1, pp. 7580, 2002.
[18] F. Demarosi, D. Soligo, G. Lodi, L. Moneghini, A. Sardella,
and A. Carrassi, Squamous cell carcinoma of the oral cavity
associated with graft versus host disease: report of a case and
review of the literature, Oral Surgery, Oral Medicine, Oral
Pathology, Oral Radiology and Endodontology, vol. 100, no. 1, pp.
6369, 2005.
[19] S. Elad, J. E. Raber-Durlacher, M. T. Brennan et al., Basic
oral care for hematologyoncology patients and hematopoietic

14

[20]

[21]

[22]

[23]

[24]

[25]

[26]

[27]

[28]

[29]

[30]

[31]

[32]

[33]

Journal of Oncology
stem cell transplantation recipients: a position paper from the
joint task force of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology
(MASCC/ISOO) and the European Society for Blood and
Marrow Transplantation (EBMT), Supportive Care in Cancer,
vol. 23, no. 1, pp. 223236, 2015.
R. Albuquerque, V. Morais, and A. Sobral, Protocolo de atendimento odontologico a pacientes oncologicos pediatricos
revisao de literatura, Revista de Odontologia da UNESP, vol. 36,
no. 3, pp. 275280, 2007.
D. Martins, M. A. Martins, and L. Seneda, Suporte odontologico ao paciente oncologico: prevencao, diagnostico, tratamento e reabilitacao das sequelas bucais, Prat Hosp, vol. 7, no.
41, pp. 166169, 2005.
M. T. Brennan, S.-B. Woo, and P. B. Lockhart, Dental treatment
planning and management in the patient who has cancer,
Dental Clinics of North America, vol. 52, no. 1, pp. 1937, 2008.
S. Elad, T. Thierer, M. Bitan, M. Y. Shapira, and C. Meyerowitz,
A decision analysis: the dental management of patients prior
to hematology cytotoxic therapy or hematopoietic stem cell
transplantation, Oral Oncology, vol. 44, no. 1, pp. 3742, 2008.
D. C. Tong and B. R. Rothwell, Antibiotic prophylaxis in
dentistry: a review and practice recommendations, Journal of
the American Dental Association, vol. 131, no. 3, pp. 366374,
2000.
M. Paiva, J. Moraes, R. De Biase, O. Batista, and M. Honorato,
Estudo retrospectivo das complicaco es orais decorrentes da
terapia antineoplasica em pacientes do Hospital Napoleao
LaureanoPB, Odontologia Clnico-Cientfica, vol. 6, no. 1, pp.
5155, 2007, http://www.scielo.br/scielo.php?script=sci nlinks
&ref=000139&pid=S1414-462X20130001000020002&lng=pt.
C. Padmini and K. Y. Bai, Oral and dental considerations in
pediatric leukemic patient, ISRN Hematology, vol. 2014, Article
ID 895721, 11 pages, 2014.
Darka, and G. Pinarli, Long-term effects
A. Avsar, M. Elli, O.
of chemotherapy on caries formation, dental development, and
salivary factors in childhood cancer survivors, Oral Surgery,
Oral Medicine, Oral Pathology, Oral Radiology and Endodontology, vol. 104, no. 6, pp. 781789, 2007.
S. Elad, S. B. Jensen, J. E. Raber-Durlacher et al., Clinical
approach in the management of oral chronic graft-versushost disease (cGVHD) in a series of specialized medical centers, Support Care Cancer, 2014, http://www.ncbi.nlm.nih.gov/
pubmed/25417041.
J. B. Epstein, J. E. Raber-Durlacher, A. Wilkins, M.-G. Chavarria, and H. Myint, Advances in hematologic stem cell transplant: an update for oral health care providers, Oral Surgery,
Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology, vol. 107, no. 3, pp. 301312, 2009.
C. Chu, A. H. Lee, L. Zheng, M. L. Mei, and G. C. Chan,
Arresting rampant dental caries with silver diamine fluoride in
a young teenager suffering from chronic oral graft versus host
disease post-bone marrow transplantation: a case report, BMC
Research Notes, vol. 7, article 3, 2014.
J. C. Atkinson, M. Grisius, and W. Massey, Salivary hypofunction and xerostomia: diagnosis and treatment, Dental Clinics of
North America, vol. 49, no. 2, pp. 309326, 2005.
M. C. Haytac, M. C. Dogan, and B. Antmen, The results
of a preventive dental program for pediatric patients with
hematologic malignancies, Oral Health & Preventive Dentistry,
vol. 2, no. 1, pp. 5965, 2004.
L. Eversole, Bleeding disorders, in Essentials of Oral Medicine,
S. Silverman, L. R. Eversole, and E. L. Truelove, Eds., pp. 6166,
BC Decker, London, UK, 2nd edition, 2001.

[34] P. Koulocheris, M. C. Metzger, M. R. Kesting, and B. HohlwegMajert, Life-threatening complications associated with acute
monocytic leukaemia after dental treatment, Australian Dental
Journal, vol. 54, no. 1, pp. 4548, 2009.
[35] J. A. Toljanic, J. F. Bedard, R. A. Larson, and J. P. Fox, A
prospective pilot study to evaluate a new dental assessment and
treatment paradigm for patients scheduled to undergo intensive
chemotherapy for cancer, Cancer, vol. 85, no. 8, pp. 18431848,
1999.
[36] B. Sheller and B. Williams, Orthodontic management of
patients with hematologic malignancies, American Journal of
Orthodontics and Dentofacial Orthopedics, vol. 109, no. 6, pp.
575580, 1996.
[37] J. E. Raber-Durlacher, A. M. G. A. Laheij, J. B. Epstein et
al., Periodontal status and bacteremia with oral viridans
streptococci and coagulase negative staphylococci in allogeneic
hematopoietic stem cell transplantation recipients: a prospective observational study, Supportive Care in Cancer, vol. 21, no.
6, pp. 16211627, 2013.
[38] F. W. G. Costa, R. R. Rodrigues, L. H. T. de Sousa et al., Local
hemostatic measures in anticoagulated patients undergoing
oral surgery. A systematized literature review, Acta Cirurgica
Brasileira, vol. 28, no. 1, pp. 7883, 2013.
[39] G. Ramstrom, S. Sindet-Pedersen, G. Hall, M. Blomback,
and U. Alander, Prevention of postsurgical bleeding in oral
surgery using tranexamic acid without dose modification of oral
anticoagulants, Journal of Oral and Maxillofacial Surgery, vol.
51, no. 11, pp. 12111216, 1993.
[40] M. J. Coetzee, The use of topical crushed tranexamic acid
tablets to control bleeding after dental surgery and from skin
ulcers in haemophilia, Haemophilia, vol. 13, no. 4, pp. 443444,
2007.
[41] A. C. R. T. Horliana, L. Chambrone, A. M. Foz et al., Dissemination of periodontal pathogens in the bloodstream after
periodontal procedures: a systematic review, PLoS ONE, vol. 9,
no. 5, Article ID e98271, 2014.
[42] C. G. Daly, D. H. Mitchell, J. E. Highfield, D. E. Grossberg, and
D. Stewart, Bacteremia due to periodontal probing: a clinical
and microbiological investigation, Journal of Periodontology,
vol. 72, no. 2, pp. 210214, 2001.
[43] D. F. Kinane, M. P. Riggio, K. F. Walker, D. MacKenzie, and
B. Shearer, Bacteraemia following periodontal procedures,
Journal of Clinical Periodontology, vol. 32, no. 7, pp. 708713,
2005.
[44] C. Daly, D. Mitchell, D. Grossberg, J. Highfield, and D. Stewart,
Bacteraemia caused by periodontal probing, Australian Dental Journal, vol. 42, no. 2, pp. 7780, 1997.
[45] A. B. Melkos, G. Massenkeil, R. Arnold, and P. A. Reichart,
Dental treatment prior to stem cell transplantation and its
influence on the posttransplantation outcome., Clinical oral
investigations, vol. 7, no. 2, pp. 113115, 2003.
[46] K. Yamagata, K. Onizawa, H. Yoshida et al., Dental management of pediatric patients undergoing hematopoietic stem cell
transplant, Pediatric Hematology and Oncology, vol. 23, no. 7,
pp. 541548, 2006.
[47] S. Abdullah and Z. Ahmad, Protocol for dental treatment
before bone marrow transplantation (BMT) in paediatric
patient, Pakistan Oral & Dental Journal, vol. 34, no. 3, pp. 399
405, 2014.
[48] National Cancer Institute (US), Posttransplantation Dental
Treatment, http://www.cancer.gov/cancertopics/pdq/supportivecare/oralcomplications/HealthProfessional/page11.

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